title: What have we learned about chronic kidney disease-mineral bone disorder from the EVOLVE and PRIMO trials?
abstract: OBJECTIVE
  The treatment of chronic kidney disease-mineral bone disorder (CKD-MBD) has traditionally focused on improvement in biochemical parameters of the disease. However, studies evaluating hard clinical end points or surrogate end points are limited.
  
  
  RESULTS
  Two randomized controlled trials have recently been published. In the EVOLVE study (Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events), cinacalcet was compared with placebo in 3883 haemodialysis patients with secondary hyperparathyroidism. The primary end point (death, myocardial infarction, unstable angina, heart failure or peripheral vascular disease) in an unadjusted intention-to-treat analysis was not significant [hazard ratio 0.93; 95% confidence interval (CI) 0.85-1.02, P=0.11]. However, the pre-specified secondary end points of an adjusted intention-to-treat analysis (hazard ratio 0.88; 95% CI 0.79-0.97, P=0.008) were significant. In the PRIMO (Paricalcitol Capsule Benefits in Renal Failure Induced Cardiac Morbidity) trial, 227 patients with CKD stage 3-4 and left ventricular hypertrophy by echocardiography were randomized to paricalcitol or placebo. The primary end point of change in left ventricular mass index by MRI after 12 months was not different between the two groups, but the prespecified end point of cardiovascular-related hospitalizations was reduced in the paricalcitol-treated group (P=0.04).
  
  
  CONCLUSIONS
  The results of these two randomized controlled trials have negative primary end points but significant secondary end points and thus require physicians to individualize therapies for the treatment of secondary hyperparathyroidism.
authors.affiliation: aIndiana University School of Medicine and Roudebush Veterans Administration Medical Center, Indianapolis, Indiana bMassachusettes General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Moe
authors.forename: Ravi
authors.initials: R
authors.lastname: Thadhani
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001851:Bone Diseases, Metabolic / Q000188:drug therapy* / Q000209:etiology; D057966:Calcimimetic Agents / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000517:prevention & control; D000069449:Cinacalcet; D004872:Ergocalciferols / Q000627:therapeutic use; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy / Q000209:etiology; D009281:Naphthalenes / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis / Q000009:adverse effects; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000188:drug therapy* / Q000628:therapy
chemical_list: D050071:Bone Density Conservation Agents; D057966:Calcimimetic Agents; D004872:Ergocalciferols; D009281:Naphthalenes; C084656:paricalcitol; D000069449:Cinacalcet